A Promising View of Kudzu Plant, Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep: Flavonoid Phytochemical Compounds, Taxonomic Data, Traditional Uses and Potential Biological Activities for Future Cosmetic Application

: Pueraria montana var. lobata is widely known as kudzu especially in Japan, China, Korea, and other Asian countries. This plant is an ingredient for traditional food and an herbal ingredient for traditional medicines, particular in Japan and China. There are a few reports on its cosmetic uses. Interestingly, many phytochemical compounds from this plant have been continuously reported, particularly ﬂavonoid compounds, which are well-known as potential bioactive ingredients for cosmetics. This work aims to illustrate promising views of kudzu plant, focusing on the diversity of ﬂavonoid phytochemical compounds, taxonomic data, traditional uses, and potential biological activities for future cosmetic applications, i.e., antioxidant, antiglycation, skin regeneration, activities.


Introduction
Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep is also known as kudzu for Asian people. This plant species belongs to the family Fabaceae. Since ancient times, the kudzu plant has been used by Asian people for various purposes, including as foods and herbal medicines and for its health and beauty benefits. A large number of its flavonoid phytochemical compounds have been reported [1][2][3][4]. In this era of modern research and innovation, the cosmetic sector is seeking for alternative choices of plant extracts and/or natural products containing potential bioactive compounds for cosmetic product development [5,6]. Flavonoids are the popular choice of those potential bioactive phytochems for cosmetic applications. Conversely, there are no reports to illustrate these local Asian plants with a view of their cosmetic potentials. Thus, we conducted this work to present a promising view of kudzu plant in terms of its taxonomic data, traditional uses, flavonoid phytochemical compounds and potential biological activities for cosmetic applications. Next, challenging perspectives and cosmetic research directions are also summed up in this work. 2 of 12 is green, and three-lobed leaflets, pubescent, are broadly ovate, 5−7 × 12−18 cm; its base is obovate to obliquely ovate, with abaxially dense hair; its apex is acuminate. It has racemose inflorescence, 14.5-39.7 cm, and bracts are linear or linear-lanceolate, light or dark purple. Its bracteoles are ovate. Its flower is papilionaceous, dark pink to dark purple, standard obovate, and 9.5-12.5 mm. Its wings are subequal to keel. Its stamen is diadelphous. Its ovary is superior, linear, and hairy. Its fruit is legumes, which are long elliptic, [8][9][10][11].5 mm × 4.5−10 cm, flattened, with brown hirsute (Figure 1 and Table 1).

Traditional Uses (Past to Present)
Kudzu is a native plant in eastern Asia and some areas of southeast Asia. Furthermore, this plant was introduced to several parts of the world and has become an invasive species in some nations, especially in the United States [21,22]. The first anecdote of kudzu was described in approximately 1000-500 BC in Shih Ching, Chinese classical poetry [7]. Kudzu is one of the most popular herbal plants in traditional oriental medicine. Two parts of kudzu have been used as herbal medicine: (1) the root, which is called Gegen or Radix Puerariae lobatae and (2) the flower, which is named Gehua or Puerariae flos. Gegen referred to the roots of P. lobata as one of the oldest herbal medicines in Chinese traditional medicine [23]. It was first written in the Shennong Bencao Jing (the Devine Husbandman's Classic of Chinese Material Medica) during the Western Han Dynasty (between 206 BC and 8 AD) for relieving fever, diarrhea, and emesis [7]. Moreover, in the classic medical book A Treatise on Fevers (Shang Han Lun), dated in 200 AD, the usage of Gegen Tang (a decoction containing kudzu root as the major component for curing neck stiffness, lack of perspiration, and aversion to air drafts) was mentioned [24]. It was employed to treat an alcohol-related problem, for example, as an anti-intoxication agent in 600 AD and an anti-dipsotropic agent in 1200 AD, as recommended by Li Shi-Zhen, the notorious physician, herbologist and acupuncturist in Chinese history [19,23]. Almost every part of kudzu has been used for many purposes. For example, leaves, buds, and sprouts have been consumed as a vegetable in Korea [25]. Their tuberous roots have been utilized as a source of starch, which is an essential material for cooking, and also used as food in Japan [26]. To date, the root of this medicinal plant is officially listed in the People's Republic of China and Japanese Pharmacopoeia for the treatment of various ailments [7]. Its flower, a showy red-purple petal, is usually mentioned in haiku, poetry, and other Japanese literature [27]. Currently, both roots and flowers of kudzu are used as a dietary supplement and functional food, including for cosmetics, because it is a rich source of phytochemicals and nutrition.

Potential Biological Activities of Flavonoids from P. montana var. lobata for Cosmetic Application
In this section, the biological activities of flavonoid phytochemical compounds from P. montana var. lobata that have potential for cosmetic applications in this recent decade will be provided. We conducted the literature search using both the present scientific name and various synonyms that represent this kudzu plant. The keyword: flavonoid, biological activity, Pueraria montana var. lobata or its synonyms have been employed. More than 111 publications were found. Then, we extracted the related publications focusing on cosmetics issues. Interestingly, 1/10 of these hundred publications met our criteria, which means that a huge number of biological activities of kudzu plant in term of the cosmetic perspective are waiting to be discovered. According to this recent work, the four major potential biological activities of flavonoids from P. montana var. lobata are highlighted as described below.

Antioxidative Activity
Bebrevska and her team investigated the major phytochemical compounds using the HPLC validation method and investigated antioxidant activity of kudzu plant from 50% ethanolic root extract in in vivo animal model. Their results indicated that the main phytochemicals of this plant is puerarin, which showed the antioxidant potential without toxicity at 10× the treatment dose (50 mg/kg puerarin) for 21 days [28], whereas the minor phytochemical compounds, daidzin, daidzein, genistin, genistein, isoflavonoids 3 -hydroxypuerarin, 6 -xylosylpuerarin, and 3 -methoxypuerarin, were also detected by HPLC analysis. In the same year, Kim and his Korea research team determined antioxidative potential of the isolated compounds and the extracts from nine medicinal plant species; the result proved that puerarin and genistein flavonoids from kudzu root contain at least a 10-fold greater total oxyradical scavenging capacity than that of glutathione [29]. After that, Xiaoming and the Chinese research group also confirmed the in vitro antioxidant potential of this plant using hydroxyl and superoxide radical scavenging assays [30]. Besides this, the antioxidant activity of this plant was also reported in its Cosmetics 2020, 7, 12 9 of 12 flowers. The Chinese research team of Han studied the isolated flavonoid phytochemical compound, 4 ,5,7-thrihydroxy-6-methoxyisoflavone-7-O-β-d-glucopyranoside, or the so-called tectoridin, as well as tectorigenin in the aglycone form, and compared them with the tectorigenin sodium sulfonate. They found that the high water-solubility and antioxidant properties of tectorigenin sodium sulfonate which is the chemical modified flavonoid are better than those of tectorigenin and tectoridin [31]. Currently, Huang, Zhang, and Xue published their work on the increasing of antioxidant activity of the main isoflavones from this plant using mixed fermentation with Monascus purpureus [32]; the antioxidant potential was determined by DPPH, OH, FRAP and total antioxidant activity. In 2019, Son and the Korea research team conducted the research comparing major phytochemical compounds and biological activities between leaves, sprouts, stems, aerial parts, and roots; the results proved that kudzu leaves are a better source of isoflavones as well as antioxidant activity [25].

Antiglycation Activity
Glycation is commonly known as an aging reaction that is naturally occurring on the skin. This process can be increased regularly or rapidly with age depending on the individual. Gasse and the American research group suggested puerarin as one of the effective antiglycation molecules from natural plant sources tested on living human skin explants [33]. In this recent decade, there have been many research teams that showed that the major phytochemical compounds, especially puerarin from kudzu root extract, exhibit the inhibitory activity on the formation of advanced glycation end products (AGEs) related to skin-aging etiology [33][34][35]. This flavonoid compound from the kudzu medicinal plant is interesting to be investigated as an alternative choice of bioactive compounds for antiaging products.

Skin Regeneration Activity
Skin regeneration is well-known for anti-skin-aging and wound healing. Growth of skin epidermal keratinocytes is associated with this process. When skin is injured, epidermal keratinocytes will migrate and proliferate with simultaneous synthesis of collagen when the skin is injured. This promotes skin proinflammatory activity and epithelialization, resulting in skin regeneration and wound healing. Kim and his Korean team conducted their research on isoflavonoids from the flower of kudzu plant, whose skin-regenerating effect was still unknown at that time [36]. They investigated the skin-regenerative potential of isoflavonoids in human epidermal keratinocytes (HaCats) and found that it induced type I and IV collagen synthesis in HaCats, and the treatment with these isoflavonoids increased sprout outgrowth in HaCats [36]. The results suggest that these phytochemical compounds may participate in skin regeneration by promoting migration, proliferation, and collagen synthesis.

Melanogenesis Inhibitory Activity
Nowadays, white, clean skin is the trend, and a part of the satisfactory appearance of many women, especially in Asia. Melanin plays a major role to determine skin color, there are many research interests focusing on anti-melanogenesis from natural sources. The research study on melanogenesis inhibitory of kudzu plant was reported using the plant name: P. thunbergiana [37], which is the synonym of P. montana var. lobate (http://www.theplantlist.org/tpl1.1/record/ild-29298, Accessed on October 14, 2019) and refers to the same kudzu plant. Han and his research team studied the aerial part of kudzu plant extract and its flavonoids potential on anti-melanogenesis in the B16F10 melanoma cell line [37]. They demonstrated that the extract from the aerial part of this plant consists of anti-melanogenesis activity in in vitro study via two mechanisms by activating Akt/GSK-3b and interrupting maturation of tyrosinase by inhibiting a-glucosidase.

Next Challenging Perspectives and Research Directions
The next challenging perspectives and research directions of kudzu plant towards the theme of cosmetic applications are listed as follows: (1) The kudzu medicinal plant is one of the potential raw plant materials for cosmetic product development. However, more research studies of this plant are required, especially about its biological activities. According to our critical review, the flavonoids biological activities of this herbal plant provided interesting results. However, there are not many studies focusing on this kudzu plant. (2) The previous research on the kudzu plant used both the accepted name Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep as well as the synonyms, for example, P. thunbergiana, to publish their works. Therefore, the researchers who are interested in conducting future research on kudzu plant should be concerned to search for its synonyms in their literature review before starting experimental designs to answer their research questions. (3) The types of flavonoid phytochemical compounds in the different parts, such as root, leaf, flower and so forth, of these medicinal plants are different, which may possibly be provided for different biological activities. This should be a point of concern for cosmetics companies to select the part that provides the most potential for expected biological activity for their cosmetic products. (4) The previous study on the toxicity of the kudzu plant mainly focuses on the extract; even both acute toxicity and subchronic toxicity studies of this plant extract indicated its safety in animal models [38]. The toxicity test of the bioactive phytochemical compounds should be confirmed before the development of cosmetic products. (5) The kudzu plant has a wide-range distribution and is easy to grow. Interestingly, there are currently no report on the geographic effect on flavonoid compounds of the kudzu plant. However, some species that are widely distributed, such as flax [6] and other economic plants were studied, and the results indicated that cultivar type, geographic site, and cultivation time influence phytochemical compounds and biological activities.

Conclusions
Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep, also known by the well-known vernacular name kudzu, has long been used as food, herbal medicine, and cosmetic ingredient in Asia since ancient times. Most of the previous works focus on the potential of this plant as food and traditional medicine, but a small number of modern research studied on the cosmetic potential of this species. Interestingly, the results from these small research numbers exhibited the potential of the kudzu plant for cosmetic applications, such as antioxidative, antiglycation, skin regeneration, and melanogenesis-inhibitory activities. Nevertheless, more research on the biological activities for cosmetic proposes should be done in future work, and the mechanism of action of the targeted biological activities should be intensively investigated to confirm its cosmetic potential. Acknowledgments: D.T. thankfully acknowledges the SAKURA Exchange Program in Science 2018 supported by The Japan Science and Technology Agency (JST) that brought her to exchange research ideas and start her research collaboration with Kanazawa University, Japan as well as Chiang Mai University, Thailand. This work is the first result from our collaboration. She also would like to express her sincere thanks to the Promotion of Science and Technology Talent Project (DPST) from the Royal Thai Government for their support for her collaborative research in Japan in the form of a post-doctoral fellowship that led her to experience chemotaxonomy and flavonoid phytochemicals, including of the kudzu plant. All the authors also thank the anonymous reviewers who provide us the valuable suggestions and comments to increase the quality of this work.